Vlaams Diergeneeskundig Tijdschrift, 2010, 79 Theme: acute in dogs and cats 99

Acute pancreatitis in dogs and cats: medical imaging, biopsy, treatment and prognosis

Acute pancreatitis bij honden en katten: medische beeldvorming, bioptname, behandeling en prognose

1I. Van den Bossche, 1D. Paepe, 2J. Saunders, 3M. Hesta, 1S. Daminet

1Department of Small Animal Medicine and Clinical Biology 2Department of Medical Imaging of Domestic Animals 3Department of Nutrition, Genetics and Ethology Faculty of Veterinary Medicine, Ghent University, Salisburylaan 133, B-9820, Merelbeke, Belgium

[email protected]

ABSTRACT

Diagnosing acute pancreatitis in dogs and cats is difficult. Abdominal ultrasonography provides specific information about the size, shape and homogeneity of the , but is very dependent on the experience of the operator and the quality of the echography machine. Abdominal radiography is less useful, while computed tomography is less practicable in veterinary patients because of the anesthesia risks, the need for experienced operators, and the high cost. Furthermore, computed tomography has low diagnostic value in cats. Biopsy of pancreatic tissue remains the gold standard. Treatment consists of fluid therapy and nutritional support, combined with pain medication, anti-emetics and antibiotics. The prognosis in dogs and cats is variable and largely depends on the clinical condition of the patient at admission. It is usually guarded, especially in cats.

SAMENVATTING

Het diagnosticeren van acute pancreatitis bij honden en katten is moeilijk. Abdominale echografie verschaft specifieke informatie over de grootte, vorm en homogeniciteit van de pancreas maar is erg afhankelijk van de ervaring van de uitvoerder en de kwaliteit van het echografietoestel. Radiografieën van het abdomen zijn minder nuttig, terwijl computertomografie minder bruikbaar is bij diergeneeskundige patiënten omwille van het anesthesierisico, de nood aan ervaren uitvoerders en de hoge kostprijs. Bovendien heeft computertomografie een lage diagnostische waarde bij de kat. De biopsie van pancreasweefsel blijft de gouden standaard. De behandeling omvat vloeistoftherapie en nutritionele ondersteuning in combinatie met pijnmedicatie, anti-emetica en antibiotica. De prognose bij de hond en de kat is variabel en afhankelijk van de klinische toestand van de patiënt op het tijdstip dat hij aangeboden wordt, maar ze is meestal gereserveerd, vooral bij katten.

INTRODUCTION MEDICAL IMAGING

In practice, acute pancreatitis is a common disorder Radiography which can be difficult to diagnose. Because of the nonspecific signs and limitations of the currently avai- Under normal circumstances, the pancreas is not vi- lable laboratory tests, medical imaging plays an im- sible on plain radiographs (Simpson and Lamb, 1995; portant role in diagnosing acute pancreatitis in dogs and Bischoff, 2003). In dogs with acute pancreatitis, in crea- cats. Because delayed therapy can lead to a fatal out- sed opacity and loss of visceral detail can be seen in the come, a rapid recognition of the disease is important. right cranial abdomen (‘ground glass’ appearance) as- This report is the second one in a series of three, which sociated with local peritonitis (Hess et al., 1998; Bi- gives a review of acute pancreatitis in dogs and cats. schoff, 2003; Ruaux, 2003) (Figures 1a and 1b). On This article will discuss the indications, as well as the ventrodorsal projections, the inflamed pancreas can advantages and disadvantages of the various medical cause a displacement of the pyloric antrum to the left, imaging techniques and of pancreatic biopsies. In ad- the descending duodenum to the right and the trans- dition, the treatment options and prognosis will be re- verse colon caudally (Simpson and Lamb, 1995; Hess viewed. et al., 1998; Bischoff, 2003; Ruaux, 2003; Mix and Jo- nes, 2006). In some patients, the proximal duodenum appears dilated and fixed (C-shaped), displaced late- 100 Vlaams Diergeneeskundig Tijdschrift, 2010, 79

Figure 1a. Loss of serosal detail in the right cranial ab- domen (arrow) on a ventrodorsal radioraphic image of a dog with acute pancreatitis. rally and dorsally, with a widening of the pyloroduo- denal angle (Bunch, 2003; Ruaux, 2003; Watson, 2004). A static gas pattern can be noted in the trans- verse colon and the descending duodenum, the wall of which can be thickened (Hess et al., 1998; Bischoff, 2003). Gastric distention suggesting gastric outlet ob- struction is another possible abnormality (Bunch, 2003). Radiographs of the thorax can show pleural ef- fusion (Bischoff, 2003) or pulmonary disease (edema Figure 1b. Lateral radiographic image of the abdomen of or pneumonia) (Hess et al., 1998). the dog seen in figure 1a. Unfortunately, in one study of fatal cases of canine pancreatitis (Hess et al., 1998), these possible abdo- abdomen can be evaluated at the same time. In addi- minal radiographic signs compatible with acute pan- tion, it is becoming more available for general practi- creatitis were seen in only 24% of the patients, whereas tioners (Watson, 2004). It is however important to un- 68% showed ultrasonographic abnormalities sugge- derline that the diagnostic value of US is strongly stive of pancreatitis. Therefore, abdominal radiography operator and machine dependent. Furthermore, the de- has a low sensitivity in diagnosing pancreatitis. In gree of pancreatic inflammation and edema also plays spite of this disadvantage, radiography offers the as- a role (Simpson and Lamb, 1995; Ruaux, 2003; Wat- sessment of other abdominal organs for ruling out dif- son, 2004; Mix and Jones, 2006). In contrast to radio- ferential diagnoses, such as intestinal foreign body. graphy, ultrasonography gives more specific informa- Furthermore, radiography is a widely and easily avai- tion about the size, shape and homogeneity of the lable technique, which remains relatively inexpensive. pancreas (Simpson and Lamb, 1995; Bunch, 2003; Radiography can be used in conjunction with abdomi- Watson, 2004). However, false negative results are nal ultrasound (Watson, 2004; Mix and Jones, 2006). possible (Ruaux, 2003), while not all lesions can be In cats with acute pancreatitis, the same radio- correlated with the clinical status of the patient (Mix graphic changes can be seen as in dogs (Gerhardt et and Jones, 2006). Therefore, it cannot be used as an ex- al., 2001; Ferreri et al., 2003). However, these signs clusion diagnostic procedure. In cats, more work has are often subtle and inconsistent (Hill and Van Winkle, been published to evaluate the sensitivity of several US 1993; Mansfield and Jones, 2001), and the most abnormalities of the pancreas. In contrast, the availa- reported features are reduced abdominal contrast (28- ble information in dogs is limited and further investi- 50%), dilated bowel loops (24-42%) and pleural gation is required. effusion (20-29%) (Gerhardt et al., 2001; Saunders et Most typically, there is a focal area of pain when al., 2002; Ferreri et al., 2003). In cats, hepatomegaly the US probe is placed over the region of the pancreas. can be seen in cases of concurrent hepatic lipidosis Due to edema, pancreatic swelling and peri-pancreatic (Akol et al., 1993). fat necrosis, the inflamed pancreas is more easy to localize than the normal pancreas (Watson, 2004). Abdominal ultrasonography Findings suggestive for acute pancreatitis in dogs include a diffusely enlarged pancreas (more than 2 cm One of the most reliable and increasingly used diag - in diameter) with hypoechoic parenchyma, hyper- nostic tools for pancreatitis in dogs and cats is ultra- echoic surrounding mesentery and generalized or local sound (US) of the abdomen. US has the advantage of peritoneal effusion (Simpson and Lamb, 1995; Hess et being non-invasive, safe and relatively low in cost. In- al., 1998; Ruaux, 2003; Mansfield, 2004; Watson, formation can be obtained immediately and the whole 2004; Mix and Jones, 2006) (Figure 2). Thickening of Vlaams Diergeneeskundig Tijdschrift, 2010, 79 101

Figure 2. Ultrasonographic image: hypoechoic enlarged Figure 3. Ultrasonographic image: hypoechoic enlarged pancreas (big arrow) lined by hyperechoic mesentery pancreas (big arrow) with several, regularly outlined (small arrow) in a dog with acute pancreatitis. hyperechoic spots (small arrow) in a cat with acute pan- creatitis.

irregular or hypoechoic pancreas and hyperechoic peripancreatic mesentery were found by Kimmel et al. (2001) in respectively 64% and 43% of the cases involving cats (Figure 3). Beyond this, more subtle and non-pancreatic changes can be diagnostically impor - tant as well. Additional ultrasonographic abnormalities in cats include abdominal effusion (31-45%), distention of the gallbladder and common bile duct (17-24%) (Figure 4), and thrombosis of the pan- creaticoduodenal vein (5%). A hyperechoic, enlarged liver consistent with hepatic lipidosis was seen in 28- 45% of cats with acute pancreatitis (Akol et al., 1993; Figure 4. Ultrasonographic image: dilation of the com- Gerhardt et al., 2001; Kimmel et al., 2001; Saunders et mon bile duct (arrow) in a cat with acute pancreatitis. al., 2002; Ferreri et al.; 2003). Less frequent findings included small hyperechoic kidneys, mesenteric the stomach or duodenal wall and dilated bile ducts lymphadenopathy, intestinal abnormalities and small can be present (Simpson and Lamb, 1995; Bunch, gallbladder with inspissated bile (Saunders et al., 2003; Watson, 2004; Mix and Jones, 2006). In one 2002). study, pancreatitis was found to be the most common cause of corrugated small intestine (especially Advanced imaging involving the duodenum) in both dogs and cats (Moon et al., 2003). Less frequently, dilatation of the pan - Computed tomography creatic duct may be detected, which is considered pathognomonic for pancreatitis in human patients, and In contrast to human medicine, where computed to- probably also in companion animals (Simpson and mography (CT) is the preferred modality for the diag - Lamb, 1995; Watson, 2004). nosis and assessment of the severity of acute pancrea- Ultrasonography is a very useful imaging technique titis, this technique has limited usefulness in veterinary in diagnosing acute pancreatitis in cats, especially patients with suspected pancreatitis (Ruaux, 2003; Mix when it is combined with other tests. However, as a and Jones, 2006). The three main reasons for this are single test, its sensitivity is controversial: depending the requirement of anesthesia to avoid movement arti- on the author cited, the sensitivity lies between 11% facts, the need for operator experience and technical en 67% (Swift et al., 2000; Gerhardt et al., 2001; skills, and the high cost (Ruaux, 2003; Mix and Jones, Forman et al., 2004). In a study by Saunders et al. 2006). However, in large practices and teaching hos- (2002), ultrasonographic evidence of acute pancreatic pitals, where availability and cost are less of an issue, necrosis was only present in 7 of 20 cats. This rela- CT can develop into a useful diagnostic step. tively low sensitivity (35%) might be attributable to In a study using CT as a diagnostic test for pan- the inappropriate adaptation of the ultrasonographic creatitis in dogs, 64% of the patients had pathologic diagnostic criteria used in dogs to cats. Indeed, the changes (Spillman et al., 2000). In two case reports in typical image of a hypoechoic pancreas with dogs, pancreatic necrosis and associated vascular com- hyperechoic mesentery often seen in dogs was only plications such as splenic vein thrombosis and renal in- present in 25 to 35% of the cats in this study and in a farction were diagnosed by contrast enhanced CT (Jae - study by Ferreri et al. (2003). However, an enlarged, ger et al., 2003). 102 Vlaams Diergeneeskundig Tijdschrift, 2010, 79

In cats, CT has a low diagnostic value. In one study are required. Because the lesions are randomly distri- by Gerhardt et al. (2001), visualization of the pancreas buted, there is no preferred site for biopsy samples un- remained difficult after intravenous administration of less gross lesions are present (Newman et al., 2004). contrast medium. In contrast to this finding, Forman Another limitation is that histologic evidence of et al. (2004) were able to visualize the pancreas in 95% pancreatic inflammation is common, even in patients of the cats (with and without pancreatitis) using not suspected of pancreatic disease. This forms a di- contrast-enhanced CT. The sensitivity is low: evidence lemma for determining the clinical relevance of in- of pancreatitis was observed in only 2 out of 10 cats flammatory lesions on surgical biopsy (Newman et with acute pancreatitis (Gerhardt et al., 2001). Further- al., 2004). Pancreatic biopsies can be obtained by la- more, the measurement of pancreatic size is influenced paroscopy or by celiotomy. The need for anesthesia is by the positioning of the patient, which can create an important disadvantage for both, because patients discrepancies in patient-to-patient measurements suspected of pancreatitis are often poor anesthetic can- (Forman et al., 2004). didates. Recently, laparoscopy has been evaluated and appears to be safe and useful for the evaluation of Magnetic resonance imaging pancreatic disease (Webb and Trott, 2008). In addition, this technique is less invasive than celiotomy. However, Several studies have been published concerning the latter technique allows a more complete exploration magnetic resonance imaging (MRI) in diagnosing of the abdomen (Mix and Jones, 2006). neuro endocrine pancreatic tumors in dogs. To the Ultrasound-guided fine-needle aspiration does not authors’ knowledge, no information is yet available require anesthesia and may reveal necrosis or inflam- about the use of this imaging technique in small mation of the pancreas. Because the pancreas is diffi- animals with acute pancreatitis. cult to visualize ultrasonographycally, the experience Based on the current knowledge, the authors sug- of the operator plays an important role (Mix and Jones, gest that abdominal US is clearly superior to CT as a 2006). first test in dogs, especially small dogs, and in cats sus- pected of pancreatitis. However, when US is negative TREATMENT AND PROGNOSIS and the patient can tolerate anesthesia, CT can be con- sidered in medium and large breed dogs. Treatment and prognosis of acute pancreatitis in dogs and cats are closely associated with the severity PANCREATIC BIOPSY AND FINE NEEDLE ASPI- of the disease (Watson, 2004). In general, the goals of RATION treatment include eliminating the underlying cause, restoring fluid and electrolyte balance, decreasing pan- Biopsy of the pancreas is considered the most relia - creatic secretion, controlling vomiting, relieving pain, ble test for diagnosing acute pancreatitis in dogs and providing nutritional support if necessary and, if pos- cats and is often used in publications as the golden sible, managing complications such as acute renal fai- standard for evaluating the accuracy (sensitivity, lure or diffuse intravascular coagulation (Bunch, 2003; specificity) of a diagnostic test (Watson, 2004; Mix Zoran, 2006). Treatment is mainly supportive. As for and Jones, 2006; Zoran, 2006, De Cock et al., 2007; other diseases, the treatment options are not always ba- Watson, 2007b). In a study by Newman et al. (2004), sed on scientific evidence and studies, but rely rather 73 pancreata from dogs presented for post-mortem on experience in practice and experience in human examination were histologically evaluated: while only medicine. Unfortunately, evidence based on properly 5.5% of them showed gross lesions suggestive of designed prospective, randomized, placebo controlled pancreatitis, 64.4% revealed microscopic evidence. So studies is currently almost nonexistent for the treatment the lack of gross lesions during exploratory celiotomy of pancreatitis in dogs and cats. However, every part of does not exclude the presence of pancreatitis, and it is the treatment can be explained by the pathologic this fact that makes clear the importance of pancreatic changes that take place in acute pancreatitis. Doses and biopsy. In the same study, acute pancreatitis was found product names of frequently used medications can be to be present in 48.9%, as defined by the presence of found in Table 1. neutrophils and pancreatic necrosis. De Cock et al. (2007) found acute pancreatitis in 15.7% of 115 cats Fluid and nutritional therapy presented for necropsy, irrespective of the cause of death. Histologic lesions were characterized by Fluid therapy and nutritional support are the cor- neutrophilic inflammation, surrounded by areas of nerstones of treating dogs and cats with acute pan- necrosis. creatitis (Bunch, 2003). Fluids will provide mainte- Biopsy is a specific technique, but not very sensi- nance requirements, reverse dehydration, replace tive (Mix and Jones, 2006; Mansfield, 2004; Zoran, ongoing losses, restore electrolyte imbalances and sup- 2006), because the pancreatic lesions can be localized port adequate tissue perfusion to avoid ischemia instead of diffuse. Newman et al. (2004) and De Cock (Bunch, 2003; Watson, 2004). Traditionally, complete et al. (2007) concluded that pancreatic inflammation pancreatic rest by starvation was recommended to occurs in discrete areas within the pancreas rather than avoid enzyme secretion and prevent further autodige- diffusely, which might suggest that multiple biopsies stion of the inflamed pancreas and peri-pancreatic tis- Vlaams Diergeneeskundig Tijdschrift, 2010, 79 103

Table 1. Frequently used medication in patients with acute pancreatitis. Classification Group Examples Product Dose Analgetics Opioid Fentanyl Fentanyl®* 1-5 µg/kg IV q 20-30min; 2-5 µg/kg/h CRI; bandage 4 µg/kg/h Opioid Butorphanol Dolorex®+ 0.1-0.5 mg/kg SC, IM or IV Dissociative anesthetic Ketamine Anesketin® 3-5 µg/kg/min CRI Anti-emetics Serotonine-inhibitor Ondansetron Zofran®* 0.5 mg/kg IV loading dose, followed by 0.5 mg/kg/h CRI for 6h or 0.5-1 mg/kg PO q 12-24h Phenotiazine Prochlorperazine Buccastem®*, 0.5-1 mg/kg PO q 8-12h Prochlorperazine EG®* 0.1-0.5 mg/kg SC, IM or IV Anti-emetic and Metoclopramide Primperan®* 0.2-0.5 mg/kg PO, SC or IM q 6-8h prokinetic Metoclopramide EG®* 1-2 mg/kg IV over 24h as CRI Neurokinin-1 Maropitant Cerenia®+ 2 mg/kg PO q 24h receptor-antagonist 1 mg/kg SC q 24h Anti-ulcer Histamine-2 blockerRanitidine Zantac®* 2 mg/kg PO, IM or IV q 8-12h medication Gastric mucosal Sucralfate Ulcogant®*, 0.5 g PO q 6-8h (< 20kg) protectant Antepsin®*, Carafate®* 1-2 g PO q 6-8h (> 20kg) Cats: 0.25 g PO q 8-12h Proton pump inhibitor Omeprazole Gastrogard®*, 0.5-1.5 mg/kg PO or IV q 24h Mepradec®*, Zanprol®* Cats: 0.75-1 mg/kg PO q 24h Omeprazole EG Maximum of 8 weeks Antibiotics Lincosamide Clindamycine Antirobe®, Clindabuc® 5.5 mg/kg PO q 12h 11 mg/kg PO q 24h Fluoroquinolone Enrofloxacin Baytril®° 2.5 mg/kg PO q 12h 5 mg/kg SC or IV q 24h Sulphonamide/ Sulphonamide/ Tribrissen 80® 15 mg/kg PO q 12h Trimethoprim Trimethoprim Aminoglycosides Amikacin Amukin®* 5-10 mg/kg SC, IM or IV q 8h 10-15 mg/kg SC, IM or IV q 24h Aminopenicillines Ampicillin Albipen-LA®, AMPI-kel® 10-20 mg/kg PO, SC, IM or IV Aminopenicillines Amoxicillin Clavubactin® associated with clavulanic acid Clavobay® beta-lactamase inhibitor 12.5 mg/kg PO q 12h Antibacterial Nitroimidazole Metronidazole Stomorgyl® 12.5 mg metronidazole and antiprotozoal (with spiramycin) + 23.4 mg spiramycine/kg PO q 24h medication

CRI: constant rate infusion *: Not registered for dogs and cats +: Not registered for cats °: Not registered for intravenous use in dogs and cats sues (Qin et al., 2002). However, now it is thought that (generally greater than 18% or 60g/1000kcal) is the feeding small amounts of food or providing another best choice for dogs, because these two ingredients type of nutritional support is beneficial, because pa- will stimulate pancreatic enzyme secretion (Simpson, tients with protein-calorie malnutrition have a worse 2006). Cats can be offered highly digestible food, prognosis (Mansfield, 2004; Watson, 2004). Indeed, the which ideally should contain high carbohydrate and uptake of nutrients prevents abnormal enterocyt meta- low to moderate fat concentrations, except when bolism, gut atrophy and bacterial translocation (Wat- concurrent mellitus is present. Because such son, 2004; Zoran, 2006). a diet is often not commercially available, the essential In dogs and cats that are alert and not dehydrated, thing is to find a diet that is well tolerated by the small amounts of water followed by small amounts of gastrointestinal tract (Zoran, 2006). Forced feeding a low-fat, high-carbohydrate diet can be presented at must be avoided (Zoran, 2007). Garbage or low- least 24 hours after the last episode of vomiting protein, high-fat diets should be avoided to prevent (Bunch, 2003; Watson, 2004). A diet low in fat (< 25g/ relapse (Simpson, 2006; Lem et al., 2008). 1000kcal) and with a moderate protein content Hospitalization and more aggressive therapy are 104 Vlaams Diergeneeskundig Tijdschrift, 2010, 79 needed in more severe cases (Williams, 2000). Patients nutrition (EIN) via a jejunostomy tube improves the presented in shock need intravenous crystalloids at integrity and function of the intestinal mucosa and shock rate (60-90 ml/kg/h), followed by or combined reduces bacterial and endotoxin translocation. with synthetic colloids at a rate of 10 to 20 ml/kg/day Furthermore, it is the most natural route for (Simpson and Lamb, 1995; Watson, 2004). Regular administering nutrients and it reduces nosocomial adjustment of fluid therapy is required (Bunch, 2003). infection, multiple organ failure and length of It is advised to monitor packed cell volume, total hospitalization (Qin et al., 2002; Qin et al., 2003; protein concentration and kidney function on a daily Wortinger, 2006). TEN also moderates the acute phase basis. Serum electrolytes should be checked daily as response and improves disease severity and clinical long as the animal is vomiting and should be outcome (Qin et al., 2002). While not evaluating supplemented if needed. Especially hypokalemia exclusively patients with pancreatitis, Chan et al. should be tightly controlled, as it can delay recovery (2002) documented that significantly more animals due to gas tro intestinal atony and contribute to receiving supplemental enteral nutrition survived mortality (Watson, 2004). compared to those receiving PPN alone. This fact A transfusion of fresh frozen plasma (FFP) (or could prove the benefits of enteral nutrition, although whole blood) can supply protease inhibitors and albu- animals that tolerate enteral nutrition could simply be min, although there is no proof of these beneficial ef- less ill. The complications of TEN include problems fects either in animals or in humans (Simpson and associated with surgery, obstruction of the tube, Lamb, 1995; Holm et al., 2003; Mansfield, 2004; Wat- aspiration pneumonia, overfeeding and refeeding son, 2004; Mansfield, 2007). Transfusion of plasma can syndrome (Delaney et al., 2006). It is important that be combined with the administration of heparin to pre- TEN be delivered into the distal jejunum, because the vent disseminated intravascular coagulation and to en- enteral secretion (such as cholecystokinin, sure pancreatic perfusion (Simpson and Lamb, 1995: secretin and gastrin) that causes pancreatic stimulation Bunch, 2003; Watson, 2004), but the benefit of this ap- is mostly located more proximally in the gastro - proach has not yet been proven (Bunch, 2003). In our intestinal tract (gastric antrum, duodenum and experience, FFP transfusions have always been tolera- proximal jejunum). Indeed, two studies (Qin et al., ted in dogs and cats with severe acute pancreatitis. 2003; Qin et al., 2007) showed that early intrajejunal If anorexia continues or if vomiting persists for 2 or nutrition (in the form of an elemental diet) does not 3 days despite anti-emetic treatment, other nutritional significantly increase pancreatic juice secretion or support is warranted (Watson, 2004). This nutritional enzyme-protein synthesis and release. Simpson (2006) support in an early stage of the disease is even more shares the opinion that enteral nutrition is superior to important in cats than in dogs, because of the risk of parenteral nutrition, but questions whether jejunal developing hepatic lipidosis (Mansfield and Jones, delivery of nutrients is necessary, because evidence 2001; Bunch, 2003; Zoran, 2006; Watson, 2007a). exists that pancreatic enzyme synthesis is down During the first days, partial peripheral parenteral regulated in dogs with acute pancreatitis. If this is nutrition (PPN) can supply about 50% of the daily indeed the case, then the benefit of enteral nutrition energy requirements in dogs and cats and can prevent would be due rather to reductions in the systemic further catabolism by supplying readily available inflammatory response and the translocation of enteric glycerol as an energy source (Watson, 2004; Wor - bacteria than to the reduction of pancreatic stimulation tinger, 2006). On a long-term basis (> 5 days), (Simpson, 2006). Furthermore, possible complications nutritional support can be delivered by total parenteral of EIN include surrounding peritonitis, reduced nutrition (TPN) via a central venous catheter (Simpson gastrointestinal motility, osmotic and and Lamb, 1995; Watson, 2007a). Both forms require vomiting, the risks of anesthesia and the difficulty of working strictly aseptically, because the solutions are placing a tube surgically (Mansfield, 2004; Watson, ideal media for the growth of bacteria and septicemia 2004; Wortinger, 2006; Zoran, 2006). A feasible is a serious complication (Delaney et al., 2006). Other alternative is the laparoscopic-assisted placement of complications include electrolyte and metabolic jejunostomy feeding tubes. This technique allows disturbances (hyperglycemia, hyperlipidemia), direct visualization of the abdominal contents and the adynamic ileus, thrombo phlebitis and the refeeding jejunostomy site. It requires smaller incisions and syndrome, a disorder involving electrolyte shifts results in decreased postoperative pain, while the associated with glucose transport following the associated complications are mild and comparable to reintroduction of food after prolonged anorexia (Qin those seen with surgical placement (Hewitt et al., et al., 2002; Qin et al., 2003; Mansfield, 2004; De- 2004). If vomiting is under control in anorectic laney et al., 2006). Although fewer complications were animals, parenteral nutrition or EIN can be replaced seen with PPN than with TPN, survival is probably by naso-esophageal, esophagostomy or gastrostomy more related to the underlying disease than to the type tube feeding, which can be used for, respectively, of nutritional support delivered (Chan et al., 2002). short-, medium- or long-term nutritional support Villous atrophy and increased intestinal permeability, (Watson, 2004). Naso-esophageal tubes are the easiest disadvantages associated with PPN and TPN, are less to place and anesthesia is not required, in contrast to of a problem with total enteral nutrition (TEN). A the two other types (Delaney et al., 2006; Wortinger, study by Qin et al. (2002) proved that early intrajejunal 2006). Vlaams Diergeneeskundig Tijdschrift, 2010, 79 105

In conclusion, despite its possible disadvantages, intestinal tract. This could cause extra pancreatic EIN should still be preferred over TPN, which must be stimulation, which can better be avoided (de la Puente- restricted to patients who do not tolerate enteral feeding Redondo et al., 2007; Mansfield, 2007). However, in (Simpson, 2006; Zoran, 2006; Watson, 2007a). patients with ileus and gastric hypomotility, which can contribute to refrac tory vomiting, this prokinetic effect Analgetics and anti-inflammatory agents can be beneficial (Zoran, 2006). Maropitant has recently been registered for dogs, in contrast to the The benefit of analgesia in pancreatitis cases should phenothiazines, serotonine-inhibitors and metoclo - not be underestimated, because most patients suffer pramide, which all require off-label use. This highly from abdominal pain. Pain relief can be achieved using specific neurokinin-1 receptor-antagonist is a strong opioids, both partial and full agonists, which have the anti-emetic that inhibits both central and peripheral advantage of causing few changes in pancreatic ducts causes of vomiting. Compared with metoclopramide, or secretions (Simpson and Lamb, 1995; Bunch, 2003; maropitant showed a higher efficacy in the treatment Mansfield, 2004; Watson, 2004). An exception to this of ongoing emesis caused by a wide range of rule is morphine, which causes spasms of the pan- underlying clinical etiologies, including pancreatitis. creatic duct (Zoran, 2006) and increased bile duct pres- Therefore, the duration of anti-emetic treatment was sure (Mansfield, 2004). A worthy alternative that also shorter with maropitant. It is well tolerated and should be considered is a constant rate infusion of a low clinically safe, and once-daily administration is dose of ketamine (dissociative anesthetic), because of appropriate (de la Puente-Redondo et al., 2007). its minimal effects on gastrointestinal motility (Watson, Compromised gastric mucosal viability and gas- 2004). During exploratory celiotomy, intra-abdominal trointestinal ulceration are side effects of pancreatitis. bupivacaine or lidocaine (local anesthetics) can be If gastrointestinal ulceration or compromised gastric used (Mansfield, 2004). mucosal viability are suspected or diagnosed, a therapy Nonsteroidal anti-inflammatory drugs (NSAIDS) with mucosal protectants (e.g. sucralfate) and hista- are absolutely contra-indicated due to their significant mine-2 (H2) blockers (e.g. ranitidine, cimetidine) side effects: gastrointestinal ulceration and prolonged should be started (Watson, 2004). Proton pump inhi- bleeding times (Watson, 2004). Furthermore, they have bitors, such as omeprazole, are good acid inhibitors the potential to evoke renal failure in animals with hy- (Watson, 2004). Omeprazole only requires once daily potension and/or shock. Just like NSAIDS, corticoste- administration, but is not registered for use in dogs or roids increase the risk for gastroduodenal ulcers. Be- cats (Ramsey, 2008). cause there is no clinical evidence that corticosteroids reduce pancreatic inflammation in small animals and Antibiotics because they impair the removal of α macroglobu- line-proteases complexes from the plasma by the reti- Since bacteria do not play a role in the pathogene- culo-endothelial system, their use should be avoided sis of acute pancreatitis in dogs and cats, and septic (Bunch, 2003; Watson, 2004; Watson, 2007b). The complications are rather rare, the benefit of routine an- only exception to this rule is their use in cats with tibiotic therapy has been called into doubt (Mansfield, acute pancreatitis and concurrent inflammatory bowel 2007). In opposition to this consideration, however, disease or lymphocytic/plasmacytic cholangiohepatitis necrotizing pancreatitis is known to be an ideal envi- (Zoran, 2006). ronment for bacterial colonization, and antibiotic tre- It has been suggested that supplementation with atment has indeed led to a better outcome in human pa- pancreatic enzymes could help in relieving postprandial tients and experimental canine cases (Watson, 2004; pain, probably due to a negative feedback mechanism, Zoran, 2006). In most cases, and especially if patients but evidence in animals is still missing (Mansfield, have fever or sepsis, parenteral broad-spectrum anti- 2004; Watson, 2004; Watson, 2007b). biotic treatment is started (Washabau, 2001; Bunch, 2003; Watson, 2004; Zoran, 2006). Holm et al. (2003) Anti-emetics and anti-ulcer medication restrict the use of antibiotics to patients with docu- mented pancreatic infection and to protracted cases of Preventing oral intake is a first step in tempering acute pancreatitis failing to respond to supportive the- acute vomiting, but administering anti-emetics is often rapy. In human patients, pancreatic infections are most necessary. Central-acting drugs, such as pheno - commonly caused by Gram-negative enteric patho- thiazines (e.g. chlorpromazine, prochlor perazine) and gens (Holm et al., 2003). serotonine-inhibitors (e.g. ondansetron, dolastron), are Antibiotics frequently used in patients with acute preferred in dogs and cats (Bunch, 2003; Watson, pancreatitis include trimethoprim-sulphonamides 2004; Zoran, 2006), although the first group can cause (TMS), aminoglycosides (e.g. amikacin) and sedation (Watson, 2004). Metoclopramide is an fluoroquinolones (e.g. enrofloxacin) (Bunch, 2003; antagonist of the dopamine (D2) receptors at the Watson, 2004). The fluoroquinolones penetrate well in chemoreceptor trigger zone. It owes its anti-emetic several tissues, including the pancreas, because they action to the fact that it produces increased tonus of are highly lipophilic drugs, while TMS is less effective the lower esophageal sphincter, accelerated emptying in the presence of necrotic tissue (Ramsey, 2008). All of the stomach and increased activity of the upper previous types of antibiotics have a bactericidal effect 106 Vlaams Diergeneeskundig Tijdschrift, 2010, 79 against Gram-negative bacteria, while TMS and velopment of abdominal complications (Mansfield et fluoroquinolones are also effective against some al., 2003). It is reliable, but has the disadvantage that Gram-positive micro-organisms (Ramsey, 2008). biopsy of pancreatic tissue to assess for necrosis is sel- Since anaerobe bacteria are not sensitive to these types dom performed ante-mortem in companion animals. of antibiotics, it is advisable to combine them with Another approach is the use of a scheme based on cli- lincosamides (e.g. clindamycine) or nitro-imidazoles nicopathologic abnormalities due to the compromise or (e.g. metronidazole) (Holm et al., 2003; Mansfield, failure of extra-pancreatic organs. In 68 cases of spon- 2007). Another option is the use of ampicillin, which taneous canine acute pancreatitis, this classification is an aminopenicillin. Its spectrum includes many correlated with outcome (Ruaux and Atwell, 1998). Gram-positive and Gram-negative aerobic organisms However, the scoring system devised did not assess de- and obligate anaerobes, but it is inactivated by finitively confirmed cases of pancreatitis and non-cli- organisms that produce beta-lactamases (Bunch, 2003; nicopathologic findings were not used. Recently, a cli- Ramsey, 2008). To avoid this disadvantage, nical severity index for dogs with acute pancreatitis has aminopenicillin can be combined with a betalacta- been developed, based on abnormalities of the cardiac mase-inhibitor. Several products are registered for and respiratory system, intestinal integrity and vascu- companion animals and have few side effects. lar forces (changes in albumin concentration and sys- tolic arterial blood pressure). Intestinal health is of Surgical treatment especially great importance in dogs with acute pan- creatitis, in particular during the period in which ente- Surgical intervention is warranted in cases of ral nutrition is lacking. This index showed a good cor- pancreatitis that are persistent or recurrent despite relation between outcome and interval from hospital medical management to confirm the diagnosis and to admission until discharge or death. The overall morta- detect neoplasia or complicating factors such as an lity rate among all dogs was 23%, while 53% of the infection (Simpson and Lamb, 1995; Simpson, 2006). dogs with the worst clinical severity index score died Other cases, such as permanent bile duct obstruction (Mansfield et al., 2008). and infected pancreatic necrosis, require surgical Because of the usually severe forms and the intervention (Simpson and Lamb, 1995; Bunch, 2003). difficult ante-mortem diagnosis, the prognosis in cats If pancreatitis is localized to a focal area, this lobe can is guarded (Bunch, 2003). Hypocalcemia (plasma be surgically removed. If surgery is performed, ionized calcium just below reference range), leuco- cultures and biopsies are indicated (Williams, 2000). penia, hypoalbuminemia, severe dehydration, tachy- In a recent study in human patients with acute cardia, tachypnea and pyrexia are known as poor pancreatitis, peritoneal lavage helped in removing prognostic signs (Hill and Van Winkle, 1993; Kimmel cytokines and enzymes (Caronna et al., 2009). Since et al., 2001; Bunch, 2003; Zoran, 2006). there are no controlled clinical studies in dogs, this technique, if used at all, should be used very cautiously CONCLUSION (Holm et al., 2003). As the clinical signs and laboratory findings in Prognosis acute pancreatitis are non-specific, medical imaging is usually needed to confirm the diagnosis and to assess The prognosis of acute pancreatitis is variable be- for concurrent diseases or complications. Currently, cause of the unpredictable nature and the wide spec- abdominal ultrasonography is the preferred test, but it trum of severity of the disease. Dogs with only one epi- requires an experienced sonographer. Further work sode of mild pancreatitis usually have a good prognosis needs to be done to evaluate more advanced imaging (Bunch, 2003). In patients with severe pancreatitis, techniques such as MRI. Although pancreatic biopsy the prognosis depends on the number of complications and histologic evaluation are very sensitive tests if (Bunch, 2003; Holm et al., 2003), but is mostly guar- multiple biopsies are taken, this is seldom used in ded to poor (Watson, 2004). Increase in trypsinogen ac- general practice because of the expense and the need tivation peptide and certain abnormalities in the blood for anesthesia. Most patients need intensive therapy analysis (such as hypoglycemia, azotemia, elevated d- and extensive monitoring to improve the chances for dimers) are considered worse prognostic indicators survival and to prevent or address complications (Simpson and Lamb, 1995). In contrast to humans, rapidly. For the most severe cases, referral to an the presence of necrosis alone cannot be used as an in- intensive care facility needs to be considered. There is dicator of poor prognosis, because it is rather the sys- an obvious need for well designed prospective studies temic complications induced by the necrosis that cause that evaluate the different aspects of the management death (Mansfield et al., 2003). Several severity scoring of pancreatitis. Hopefully, this will lead to a better systems have been described in canine patients with prognosis in the future. acute pancreatitis. 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